Department of Surgery, University of Alabama at Birmingham, Birmingham, AL.
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.
J Pediatr Surg. 2019 Jun;54(6):1206-1213. doi: 10.1016/j.jpedsurg.2019.02.029. Epub 2019 Feb 28.
Hepatoblastoma is the most common primary liver cancer of childhood and has few prognostic indicators. We have previously shown that Proviral Integration site for Moloney murine leukemia virus (PIM3) kinase decreased hepatoblastoma tumorigenicity. We sought to determine the effect of PIM3 overexpression on hepatoblastoma cells and whether expression of PIM3 correlated with patient/tumor characteristics or survival.
The hepatoblastoma cell line, HuH6, and patient-derived xenograft, COA67, were utilized. Viability, proliferation, migration, sphere formation, and tumor growth in mice were assessed in PIM3-overexpressing cells. Immunohistochemistry was performed for PIM3 on patient samples. Correlation between stain score and clinical/pathologic characteristics was assessed.
PIM3 overexpression rescued the anti-proliferative effect observed with PIM3 knockdown. Sphere formation was increased in PIM3 overexpressing cells. Cells with PIM3 overexpression yielded larger tumors than those with empty vector. Seventy-four percent of samples expressed PIM3. There was no statistical difference in patient characteristics between subjects with strong versus weak PIM3 staining, but patients with strong PIM3 staining had decreased survival.
PIM3 expression plays a role in hepatoblastoma tumorigenesis. PIM3 was present in the majority of hepatoblastomas and higher PIM3 expression correlated with decreased survival. PIM3 warrants investigation as a therapeutic target and prognostic marker for hepatoblastoma.
肝母细胞瘤是儿童最常见的原发性肝癌，其预后指标很少。我们之前已经表明，莫洛尼鼠白血病病毒（PIM3）激酶的前病毒整合位点（Proviral Integration site for Moloney murine leukemia virus (PIM3)）降低了肝母细胞瘤的致瘤性。我们试图确定 PIM3 过表达对肝母细胞瘤细胞的影响，以及 PIM3 的表达是否与患者/肿瘤特征或生存相关。
使用肝母细胞瘤细胞系 HuH6 和患者来源的异种移植 COA67。在过表达 PIM3 的细胞中评估细胞活力、增殖、迁移、球体形成和小鼠肿瘤生长。对患者样本进行 PIM3 免疫组织化学染色。评估染色评分与临床/病理特征之间的相关性。
PIM3 过表达挽救了在 PIM3 敲低时观察到的抗增殖作用。过表达 PIM3 的细胞中球体形成增加。过表达 PIM3 的细胞产生的肿瘤比空载体的细胞大。74%的样本表达 PIM3。在具有强 versus 弱 PIM3 染色的患者之间，患者特征没有统计学差异，但具有强 PIM3 染色的患者生存时间缩短。
PIM3 表达在肝母细胞瘤发生中起作用。PIM3 存在于大多数肝母细胞瘤中，较高的 PIM3 表达与生存时间缩短相关。PIM3 有望成为肝母细胞瘤的治疗靶点和预后标志物。
